KCa3.1 channels modulate the processing of noxious chemical stimuli in mice

Neuropharmacology. 2017 Oct:125:386-395. doi: 10.1016/j.neuropharm.2017.08.021. Epub 2017 Aug 18.

Abstract

Intermediate conductance calcium-activated potassium channels (KCa3.1) have been recently implicated in pain processing. However, the functional role and localization of KCa3.1 in the nociceptive system are largely unknown. We here characterized the behavior of mice lacking KCa3.1 (KCa3.1-/-) in various pain models and analyzed the expression pattern of KCa3.1 in dorsal root ganglia (DRG) and the spinal cord. KCa3.1-/- mice demonstrated normal behavioral responses in models of acute nociceptive, persistent inflammatory, and persistent neuropathic pain. However, their behavioral responses to noxious chemical stimuli such as formalin and capsaicin were increased. Accordingly, formalin-induced nociceptive behavior was increased in wild-type mice after administration of the KCa3.1 inhibitor TRAM-34. In situ hybridization experiments detected KCa3.1 in most DRG satellite glial cells, in a minority of DRG neurons, and in ependymal cells lining the central canal of the spinal cord. Together, our data point to a specific inhibitory role of KCa3.1 for the processing of noxious chemical stimuli.

Keywords: KCa3.1; Pain; Potassium channel; SK4; Satellite glial cells; TRAM-34.

MeSH terms

  • Animals
  • Calcitonin Gene-Related Peptide / metabolism
  • Cells, Cultured
  • Ependyma / drug effects
  • Ependyma / metabolism
  • Ependyma / pathology
  • Female
  • Ganglia, Spinal / drug effects
  • Ganglia, Spinal / metabolism*
  • Ganglia, Spinal / pathology
  • Inflammation / metabolism
  • Inflammation / pathology
  • Intermediate-Conductance Calcium-Activated Potassium Channels / antagonists & inhibitors
  • Intermediate-Conductance Calcium-Activated Potassium Channels / deficiency
  • Intermediate-Conductance Calcium-Activated Potassium Channels / genetics
  • Intermediate-Conductance Calcium-Activated Potassium Channels / metabolism*
  • Male
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Neuralgia / metabolism*
  • Neuralgia / pathology
  • Neuroglia / drug effects
  • Neuroglia / metabolism
  • Neuroglia / pathology
  • Neurons / drug effects
  • Neurons / metabolism
  • Neurons / pathology
  • Nociceptive Pain / metabolism*
  • Nociceptive Pain / pathology
  • Pain Threshold / drug effects
  • Pain Threshold / physiology
  • Potassium Channel Blockers / pharmacology
  • Pyrazoles / pharmacology
  • Sciatic Nerve / injuries
  • Sensory System Agents
  • Spinal Cord / drug effects
  • Spinal Cord / metabolism
  • Spinal Cord / pathology

Substances

  • Intermediate-Conductance Calcium-Activated Potassium Channels
  • Kcnn4 protein, mouse
  • Potassium Channel Blockers
  • Pyrazoles
  • Sensory System Agents
  • TRAM 34
  • Calcitonin Gene-Related Peptide